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Overview of the 30-year history of metabolic engineering
< Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST > A research team comprised of Gi Bae Kim, Dr. So Young Choi, Dr. In Jin Cho, Da-Hee Ahn, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST reported the 30-year history of metabolic engineering, highlighting examples of recent progress in the field and contributions to sustainability and health. Their paper “Metabolic engineering for sustainability and health” was published online in the 40th anniversary special issue of Trends in Biotechnology on January 10, 2023. Metabolic engineering, a discipline of engineering that modifies cell phenotypes through molecular and genetic-level manipulations to improve cellular activities, has been studied since the early 1990s, and has progressed significantly over the past 30 years. In particular, metabolic engineering has enabled the engineering of microorganisms for the development of microbial cell factories capable of efficiently producing chemicals and materials as well as degrading recalcitrant contaminants. This review article revisited how metabolic engineering has advanced over the past 30 years, from the advent of genetic engineering techniques such as recombinant DNA technologies to recent breakthroughs in systems metabolic engineering and data science aided by artificial intelligence. The research team highlighted momentous events and achievements in metabolic engineering, providing both trends and future directions in the field. Metabolic engineering’s contributions to bio-based sustainable chemicals and clean energy, health, and bioremediation were also reviewed. Finally, the research team shared their perspectives on the future challenges impacting metabolic engineering than must be overcome in order to achieve advancements in sustainability and health. Distinguished Professor Sang Yup Lee said, “Replacing fossil resource-based chemical processes with bio-based sustainable processes for the production of chemicals, fuels, and materials using metabolic engineering has become our essential task for the future. By looking back on the 30+ years of metabolic engineering, we aimed to highlight the contributions of metabolic engineering to achieve sustainability and good health.” He added, “Metabolic engineering will play an increasingly important role as a key solution to the climate crisis, environmental pollution, food and energy shortages, and health problems in aging societies.” < Figure: Metabolic Engineering Timeline >
Phage resistant Escherichia coli strains developed to reduce fermentation failure
A genome engineering-based systematic strategy for developing phage resistant Escherichia coli strains has been successfully developed through the collaborative efforts of a team led by Professor Sang Yup Lee, Professor Shi Chen, and Professor Lianrong Wang. This study by Xuan Zou et al. was published in Nature Communications in August 2022 and featured in Nature Communications Editors’ Highlights. The collaboration by the School of Pharmaceutical Sciences at Wuhan University, the First Affiliated Hospital of Shenzhen University, and the KAIST Department of Chemical and Biomolecular Engineering has made an important advance in the metabolic engineering and fermentation industry as it solves a big problem of phage infection causing fermentation failure. Systems metabolic engineering is a highly interdisciplinary field that has made the development of microbial cell factories to produce various bioproducts including chemicals, fuels, and materials possible in a sustainable and environmentally friendly way, mitigating the impact of worldwide resource depletion and climate change. Escherichia coli is one of the most important chassis microbial strains, given its wide applications in the bio-based production of a diverse range of chemicals and materials. With the development of tools and strategies for systems metabolic engineering using E. coli, a highly optimized and well-characterized cell factory will play a crucial role in converting cheap and readily available raw materials into products of great economic and industrial value. However, the consistent problem of phage contamination in fermentation imposes a devastating impact on host cells and threatens the productivity of bacterial bioprocesses in biotechnology facilities, which can lead to widespread fermentation failure and immeasurable economic loss. Host-controlled defense systems can be developed into effective genetic engineering solutions to address bacteriophage contamination in industrial-scale fermentation; however, most of the resistance mechanisms only narrowly restrict phages and their effect on phage contamination will be limited. There have been attempts to develop diverse abilities/systems for environmental adaptation or antiviral defense. The team’s collaborative efforts developed a new type II single-stranded DNA phosphorothioation (Ssp) defense system derived from E. coli 3234/A, which can be used in multiple industrial E. coli strains (e.g., E. coli K-12, B and W) to provide broad protection against various types of dsDNA coliphages. Furthermore, they developed a systematic genome engineering strategy involving the simultaneous genomic integration of the Ssp defense module and mutations in components that are essential to the phage life cycle. This strategy can be used to transform E. coli hosts that are highly susceptible to phage attack into strains with powerful restriction effects on the tested bacteriophages. This endows hosts with strong resistance against a wide spectrum of phage infections without affecting bacterial growth and normal physiological function. More importantly, the resulting engineered phage-resistant strains maintained the capabilities of producing the desired chemicals and recombinant proteins even under high levels of phage cocktail challenge, which provides crucial protection against phage attacks. This is a major step forward, as it provides a systematic solution for engineering phage-resistant bacterial strains, especially industrial bioproduction strains, to protect cells from a wide range of bacteriophages. Considering the functionality of this engineering strategy with diverse E. coli strains, the strategy reported in this study can be widely extended to other bacterial species and industrial applications, which will be of great interest to researchers in academia and industry alike. Fig. A schematic model of the systematic strategy for engineering phage-sensitive industrial E. coli strains into strains with broad antiphage activities. Through the simultaneous genomic integration of a DNA phosphorothioation-based Ssp defense module and mutations of components essential for the phage life cycle, the engineered E. coli strains show strong resistance against diverse phages tested and maintain the capabilities of producing example recombinant proteins, even under high levels of phage cocktail challenge.
Interactive Map of Metabolical Synthesis of Chemicals
An interactive map that compiled the chemicals produced by biological, chemical and combined reactions has been distributed on the web - A team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, organized and distributed an all-inclusive listing of chemical substances that can be synthesized using microorganisms - It is expected to be used by researchers around the world as it enables easy assessment of the synthetic pathway through the web. A research team comprised of Woo Dae Jang, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported an interactive metabolic map of bio-based chemicals. Their research paper “An interactive metabolic map of bio-based chemicals” was published online in Trends in Biotechnology on August 10, 2022. As a response to rapid climate change and environmental pollution, research on the production of petrochemical products using microorganisms is receiving attention as a sustainable alternative to existing methods of productions. In order to synthesize various chemical substances, materials, and fuel using microorganisms, it is necessary to first construct the biosynthetic pathway toward desired product by exploration and discovery and introduce them into microorganisms. In addition, in order to efficiently synthesize various chemical substances, it is sometimes necessary to employ chemical methods along with bioengineering methods using microorganisms at the same time. For the production of non-native chemicals, novel pathways are designed by recruiting enzymes from heterologous sources or employing enzymes designed though rational engineering, directed evolution, or ab initio design. The research team had completed a map of chemicals which compiled all available pathways of biological and/or chemical reactions that lead to the production of various bio-based chemicals back in 2019 and published the map in Nature Catalysis. The map was distributed in the form of a poster to industries and academia so that the synthesis paths of bio-based chemicals could be checked at a glance. The research team has expanded the bio-based chemicals map this time in the form of an interactive map on the web so that anyone with internet access can quickly explore efficient paths to synthesize desired products. The web-based map provides interactive visual tools to allow interactive visualization, exploration, and analysis of complex networks of biological and/or chemical reactions toward the desired products. In addition, the reported paper also discusses the production of natural compounds that are used for diverse purposes such as food and medicine, which will help designing novel pathways through similar approaches or by exploiting the promiscuity of enzymes described in the map. The published bio-based chemicals map is also available at http://systemsbiotech.co.kr. The co-first authors, Dr. Woo Dae Jang and Ph.D. student Gi Bae Kim, said, “We conducted this study to address the demand for updating the previously distributed chemicals map and enhancing its versatility.” “The map is expected to be utilized in a variety of research and in efforts to set strategies and prospects for chemical production incorporating bio and chemical methods that are detailed in the map.” Distinguished Professor Sang Yup Lee said, “The interactive bio-based chemicals map is expected to help design and optimization of the metabolic pathways for the biosynthesis of target chemicals together with the strategies of chemical conversions, serving as a blueprint for developing further ideas on the production of desired chemicals through biological and/or chemical reactions.” The interactive metabolic map of bio-based chemicals.
Metabolically Engineered Bacterium Produces Lutein
A research group at KAIST has engineered a bacterial strain capable of producing lutein. The research team applied systems metabolic engineering strategies, including substrate channeling and electron channeling, to enhance the production of lutein in an engineered Escherichia coli strain. The strategies will be also useful for the efficient production of other industrially important natural products used in the food, pharmaceutical, and cosmetic industries. Figure: Systems metabolic engineering was employed to construct and optimize the metabolic pathways for lutein production, and substrate channeling and electron channeling strategies were additionally employed to increase the production of the lutein with high productivity. Lutein is classified as a xanthophyll chemical that is abundant in egg yolk, fruits, and vegetables. It protects the eye from oxidative damage from radiation and reduces the risk of eye diseases including macular degeneration and cataracts. Commercialized products featuring lutein are derived from the extracts of the marigold flower, which is known to harbor abundant amounts of lutein. However, the drawback of lutein production from nature is that it takes a long time to grow and harvest marigold flowers. Furthermore, it requires additional physical and chemical-based extractions with a low yield, which makes it economically unfeasible in terms of productivity. The high cost and low yield of these bioprocesses has made it difficult to readily meet the demand for lutein. These challenges inspired the metabolic engineers at KAIST, including researchers Dr. Seon Young Park, Ph.D. Candidate Hyunmin Eun, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team’s study entitled “Metabolic engineering of Escherichia coli with electron channeling for the production of natural products” was published in Nature Catalysis on August 5, 2022. This research details the ability to produce lutein from E. coli with a high yield using a cheap carbon source, glycerol, via systems metabolic engineering. The research group focused on solving the bottlenecks of the biosynthetic pathway for lutein production constructed within an individual cell. First, using systems metabolic engineering, which is an integrated technology to engineer the metabolism of a microorganism, lutein was produced when the lutein biosynthesis pathway was introduced, albeit in very small amounts. To improve the productivity of lutein production, the bottleneck enzymes within the metabolic pathway were first identified. It turned out that metabolic reactions that involve a promiscuous enzyme, an enzyme that is involved in two or more metabolic reactions, and electron-requiring cytochrome P450 enzymes are the main bottleneck steps of the pathway inhibiting lutein biosynthesis. To overcome these challenges, substrate channeling, a strategy to artificially recruit enzymes in physical proximity within the cell in order to increase the local concentrations of substrates that can be converted into products, was employed to channel more metabolic flux towards the target chemical while reducing the formation of unwanted byproducts. Furthermore, electron channeling, a strategy similar to substrate channeling but differing in terms of increasing the local concentrations of electrons required for oxidoreduction reactions mediated by P450 and its reductase partners, was applied to further streamline the metabolic flux towards lutein biosynthesis, which led to the highest titer of lutein production achieved in a bacterial host ever reported. The same electron channeling strategy was successfully applied for the production of other natural products including nootkatone and apigenin in E. coli, showcasing the general applicability of the strategy in the research field. “It is expected that this microbial cell factory-based production of lutein will be able to replace the current plant extraction-based process,” said Dr. Seon Young Park, the first author of the paper. She explained that another important point of the research is that integrated metabolic engineering strategies developed from this study can be generally applicable for the efficient production of other natural products useful as pharmaceuticals or nutraceuticals. “As maintaining good health in an aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” explained Distinguished Professor Sang Yup Lee. This work was supported by the Cooperative Research Program for Agriculture Science & Technology Development funded by the Rural Development Administration of Korea, with further support from the Development of Next-generation Biorefinery Platform Technologies for Leading Bio-based Chemicals Industry Project and by the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project of the National Research Foundation funded by the Ministry of Science and ICT of Korea.
VP Sang Yup Lee Receives Honorary Doctorate from DTU
Vice President for Research, Distinguished Professor Sang Yup Lee at the Department of Chemical & Biomolecular Engineering, was awarded an honorary doctorate from the Technical University of Denmark (DTU) during the DTU Commemoration Day 2022 on April 29. The event drew distinguished guests, students, and faculty including HRH The Crown Prince Frederik Andre Henrik Christian and DTU President Anders Bjarklev. Professor Lee was recognized for his exceptional scholarship in the field of systems metabolic engineering, which led to the development of microcell factories capable of producing a wide range of fuels, chemicals, materials, and natural compounds, many for the first time. Professor Lee said in his acceptance speech that KAIST’s continued partnership with DTU in the field of biotechnology will lead to significant contributions in the global efforts to respond to climate change and promote green growth. DTU CPO and CSO Dina Petronovic Nielson, who heads DTU Biosustain, also lauded Professor Lee saying, “It is not only a great honor for Professor Lee to be induced at DTU but also great honor for DTU to have him.” Professor Lee also gave commemorative lectures at DTU Biosustain in Lingby and the Bio Innovation Research Institute at the Novo Nordisk Foundation in Copenhagen while in Denmark. DTU, one of the leading science and technology universities in Europe, has been awarding honorary doctorates since 1921, including to Nobel laureate in chemistry Professor Frances Arnold at Caltech. Professor Lee is the first Korean to receive an honorary doctorate from DTU.
Distinguished Professor Sukbok Chang Named the 2022 Ho-Am Laureate
Distinguished Professor Sukbok Chang from the Department of Chemistry was named the awardee of the Ho-Am Prize in the fields of chemistry and life sciences. The award has recognized the most distinguished scholars, individuals, and organizations in physics and mathematics, chemistry and life sciences, engineering, medicine, arts, and community service in honor of the late founder of Samsung Group Byong-Chul Lee, whose penname is Ho-Am. The awards ceremony will be held on May 31 and awardees will receive 300 million KRW in prize money. Professor Chang became the fourth KAIST Ho-Am laureate following Distinguished Professor Sang Yup Lee in engineering in 2014, Distinguished Professor Jun Ho Oh in engineering in 2016, and Distinguished Professor Gou Young Koh in medicine in 2018. Professor Chang is a renowned chemist who has made pioneering research in the area of transition metal catalysis for organic transformations. Professor Chang is also one of the Highly Cited Researchers who rank in the top 1% of citations by field and publication year in the Web of Science citation index. He has made the list seven years in a row from 2016. Professor Chang has developed a range of new and impactful C-H bond functionalization reactions. By using his approaches, value-added molecules can be readily produced from chemical feedstocks, representatively hydrocarbons and (hetero)arenes. His research team elucidated fundamental key mechanistic aspects in the course of the essential C-H bond activation process of unreactive starting materials. He was able to utilize the obtained mechanistic understanding for the subsequent catalyst design to develop more efficient and highly (stereo)selective catalytic reactions. Among the numerous contributions he made, the design of new mechanistic approaches toward metal nitrenoid transfers are of especially high impact to the chemical community. Indeed, a series of important transition metal catalyst systems were developed by Professor Chang to enable the direct and selective C-H amidation of unreactive organic compounds, thereby producing aminated compounds that have important applicability in synthetic, medicinal, and materials science. He has also pioneered in the area of asymmetric C-H amination chemistry by creatively devising various types of chiral transition metal catalyst systems, and his team proved for the first time that chiral lactam compounds can be obtained at an excellent level of stereoselectivity. Another significant contribution of Professor. Chang was the introduction of dioxazolones as a robust but highly reactive source of acyl nitrenoids for the catalytic C-H amidation reactions, and this reagent is now broadly utilized in synthetic chemistry worldwide. Professor Chang also leads a research group in the Center for Catalytic Hydrocarbon Functionalizations at the Institute for Basic Science.
Five Projects Ranked in the Top 100 for National R&D Excellence
Five KAIST research projects were selected as the 2021 Top 100 for National R&D Excellence by the Ministry of Science and ICT and the Korea Institute of Science & Technology Evaluation and Planning. The five projects are:-The development of E. coli that proliferates with only formic acid and carbon dioxide by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering -An original reverse aging technology that restores an old human skin cell into a younger one by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering-The development of next-generation high-efficiency perovskite-silicon tandem solar cells by Professor Byungha Shin from the Department of Materials Science and Engineering-Research on the effects of ultrafine dust in the atmosphere has on energy consumption by Professor Jiyong Eom from the School of Business and Technology Management-Research on a molecular trigger that controls the phase transformation of bio materials by Professor Myungchul Kim from the Department of Bio and Brain Engineering Started in 2006, an Evaluation Committee composed of experts in industries, universities, and research institutes has made the preliminary selections of the most outstanding research projects based on their significance as a scientific and technological development and their socioeconomic effects. The finalists went through an open public evaluation. The final 100 studies are from six fields: 18 from mechanics & materials, 26 from biology & marine sciences, 19 from ICT & electronics, 10 from interdisciplinary research, and nine from natural science and infrastructure. The selected 100 studies will receive a certificate and an award plaque from the minister of MSIT as well as additional points for business and institutional evaluations according to appropriate regulations, and the selected researchers will be strongly recommended as candidates for national meritorious awards. In particular, to help the 100 selected research projects become more accessible for the general public, their main contents will be provided in a free e-book ‘The Top 100 for National R&D Excellence of 2021’ that will be available from online booksellers.
3D Visualization and Quantification of Bioplastic PHA in a Living Bacterial Cell
3D holographic microscopy leads to in-depth analysis of bacterial cells accumulating the bacterial bioplastic, polyhydroxyalkanoate (PHA) A research team at KAIST has observed how bioplastic granule is being accumulated in living bacteria cells through 3D holographic microscopy. Their 3D imaging and quantitative analysis of the bioplastic ‘polyhydroxyalkanoate’ (PHA) via optical diffraction tomography provides insights into biosynthesizing sustainable substitutes for petroleum-based plastics. The bio-degradable polyester polyhydroxyalkanoate (PHA) is being touted as an eco-friendly bioplastic to replace existing synthetic plastics. While carrying similar properties to general-purpose plastics such as polyethylene and polypropylene, PHA can be used in various industrial applications such as container packaging and disposable products. PHA is synthesized by numerous bacteria as an energy and carbon storage material under unbalanced growth conditions in the presence of excess carbon sources. PHA exists in the form of insoluble granules in the cytoplasm. Previous studies on investigating in vivo PHA granules have been performed by using fluorescence microscopy, transmission electron microscopy (TEM), and electron cryotomography. These techniques have generally relied on the statistical analysis of multiple 2D snapshots of fixed cells or the short-time monitoring of the cells. For the TEM analysis, cells need to be fixed and sectioned, and thus the investigation of living cells was not possible. Fluorescence-based techniques require fluorescence labeling or dye staining. Thus, indirect imaging with the use of reporter proteins cannot show the native state of PHAs or cells, and invasive exogenous dyes can affect the physiology and viability of the cells. Therefore, it was difficult to fully understand the formation of PHA granules in cells due to the technical limitations, and thus several mechanism models based on the observations have been only proposed. The team of metabolic engineering researchers led by Distinguished Professor Sang Yup Lee and Physics Professor YongKeun Park, who established the startup Tomocube with his 3D holographic microscopy, reported the results of 3D quantitative label-free analysis of PHA granules in individual live bacterial cells by measuring the refractive index distributions using optical diffraction tomography. The formation and growth of PHA granules in the cells of Cupriavidus necator, the most-studied native PHA (specifically, poly(3-hydroxybutyrate), also known as PHB) producer, and recombinant Escherichia coli harboring C. necator PHB biosynthesis pathway were comparatively examined. From the reconstructed 3D refractive index distribution of the cells, the team succeeded in the 3D visualization and quantitative analysis of cells and intracellular PHA granules at a single-cell level. In particular, the team newly presented the concept of “in vivo PHA granule density.” Through the statistical analysis of hundreds of single cells accumulating PHA granules, the distinctive differences of density and localization of PHA granules in the two micro-organisms were found. Furthermore, the team identified the key protein that plays a major role in making the difference that enabled the characteristics of PHA granules in the recombinant E. coli to become similar to those of C. necator. The research team also presented 3D time-lapse movies showing the actual processes of PHA granule formation combined with cell growth and division. Movies showing the living cells synthesizing and accumulating PHA granules in their native state had never been reported before. Professor Lee said, “This study provides insights into the morphological and physical characteristics of in vivo PHA as well as the unique mechanisms of PHA granule formation that undergo the phase transition from soluble monomers into the insoluble polymer, followed by granule formation. Through this study, a deeper understanding of PHA granule formation within the bacterial cells is now possible, which has great significance in that a convergence study of biology and physics was achieved. This study will help develop various bioplastics production processes in the future.” This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (Grants NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) and the Bio & Medical Technology Development Program (Grant No. 2021M3A9I4022740) from the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea to S.Y.L. This work was also supported by the KAIST Cross-Generation Collaborative Laboratory project. -PublicationSo Young Choi, Jeonghun Oh, JaeHwang Jung, YongKeun Park, and Sang Yup Lee. Three-dimensional label-free visualization and quantification of polyhydroxyalkanoates in individualbacterial cell in its native state. PNAS(https://doi.org./10.1073/pnas.2103956118) -ProfileDistinguished Professor Sang Yup LeeMetabolic Engineering and Synthetic Biologyhttp://mbel.kaist.ac.kr/ Department of Chemical and Biomolecular Engineering KAIST Endowed Chair Professor YongKeun ParkBiomedical Optics Laboratoryhttps://bmokaist.wordpress.com/ Department of PhysicsKAIST
VP Sang Yup Lee Honored with the Pony Chung Innovation Award
Vice President for Research Sang Yup Lee became the recipient of the Innovation Award by the Pony Chung Foundation that was established to honor the late Se-yung Chung, the former chairman of Hyundai Development Company. He will receive 200 million KRW in prize money. Chairman Chung developed Korea’s first domestically manufactured automobile, ‘Pony,’ in the mid-1970s that became the cornerstone of Korea’s auto industry today. Distinguished Professor Lee, from the Department of Chemical and Biomolecular Engineering, is a pioneering scholar in the field of systems metabolic engineering who developed various micro-organisms for producing a wide range of fuels, chemicals, materials, and natural compounds. He recently was elected as a foreign member of the Royal Society in the UK and is the first Korean ever elected into the National Academy of Inventors (NAI) in the US as well as one of 13 scholars elected as an International Member of both the National Academy of Sciences (NAS) and the National Academy of Engineering (NAE) in the US.
Repurposed Drugs Present New Strategy for Treating COVID-19
Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS). Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3. Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives. The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds. The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected. “We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST. “The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee. This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326). -PublicationWoo Dae Jang, Sangeun Jeon, Seungtaek Kim, and Sang Yup Lee. Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay. Proc. Natl. Acad. Sci. U.S.A. (https://doi/org/10.1073/pnas.2024302118) -ProfileDistinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
Krafton Matches Alumni Donations to Raise 11 Billion KRW for SW Developers
Alumni donations from the School of Computing, including Baemin and Devsisters, continue to grow Alumni from the KAIST School of Computing who are current and former developers at the leading game company Krafton, established by KAIST alumna Byung-Gyu Chang, made an agreement to help raise 11 billion KRW during a ceremony on June 4. The funds raised in the matching grant will be used to nurture software developers. Krafton Chairman Chang donated 10 billion won last January. His donation inspired other alumni working at Krafton as well as its former developers. Eleven KAIST alumni raised 5.5 billion KRW in two months and discussed the matching grant idea with Chairman Chang. The Krafton matching grant ceremony was attended by President Kwang Hyung Lee, Provost and Executive Vice President Seung Seob Lee, Vice President for Research Sang Yup Lee, Head of the School of Computing Sukyoung Ryu, Krafton Chairman Byung-gyu Chang, and KAIST alumnus from Krafton Seung-woo Shin. Other alumni donors including Krafton CEO Changhan Kim joined the ceremony online. Krafton CEO Changhan Kim said, “Just as our alma mater played an important role in growing our company, we hope that our donation could help support good developers. This will not only help our company, but advance our industry.” KAIST and Krafton also signed a business agreement to foster competitive developers. Krafton said it plans to continue giving back to society through the matching grant program. Head of the School of Computing Sukyoung Ryu thanked Chairman Chang and alumni who took part in the fund raising, saying, “To take the lead in rapidly changing computer technology, we desperately need more top students, faculty members, and facilities. We need more resources and infrastructure for interdisciplinary research.” The School of Computing has seen significant growth recently. Its number of undergraduate students has increased from 450 in 2016 to more than 900 in 2021. With this donation, the school will expand its current buildings to provide diverse educational and mentoring programs in more spacious facilities. Seung-woo Shin (Class of ’92), who joined Krafton’s matching grant, said, “I have always been thankful for the people I met and what I learned at KAIST. I was moved by the idea of giving back to the school.” Seong-jung Ryu (Class of ’97) said, “This donation reminded me of the good times I had back then. I thought it was crucial that the department’s facilities be extended, so I naturally wanted to take part.” Alumni donations, especially from the School of Computing, have also continued to grow more recently. Woowa Brothers Corp. CEO Beom-Jun Kim, the developer of the meal delivery app ‘Baemin’ donated 100 million KRW in April. Baemin became the most used app in the country during the COVID-19 pandemic. He explained, “I have been thinking about ways to give something to the next generation, rather than ‘paying back’ those who helped me in the past.” Encouraged by Baemin’s donation, alumni couple Ha-Yeon Seo and Dong-Hun Hahn from the School of Computing and eleven alumni engineers working at Devsisters Corp. also followed suit.
Natural Rainbow Colorants Microbially Produced
Integrated strategies of systems metabolic engineering and membrane engineering led to the production of natural rainbow colorants comprising seven natural colorants from bacteria for the first time A research group at KAIST has engineered bacterial strains capable of producing three carotenoids and four violacein derivatives, completing the seven colors in the rainbow spectrum. The research team integrated systems metabolic engineering and membrane engineering strategies for the production of seven natural rainbow colorants in engineered Escherichia coli strains. The strategies will be also useful for the efficient production of other industrially important natural products used in the food, pharmaceutical, and cosmetic industries. Colorants are widely used in our lives and are directly related to human health when we eat food additives and wear cosmetics. However, most of these colorants are made from petroleum, causing unexpected side effects and health problems. Furthermore, they raise environmental concerns such as water pollution from dyeing fabric in the textiles industry. For these reasons, the demand for the production of natural colorants using microorganisms has increased, but could not be readily realized due to the high cost and low yield of the bioprocesses. These challenges inspired the metabolic engineers at KAIST including researchers Dr. Dongsoo Yang and Dr. Seon Young Park, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team reported the study entitled “Production of rainbow colorants by metabolically engineered Escherichia coli” in Advanced Science online on May 5. It was selected as the journal cover of the July 7 issue. This research reports for the first time the production of rainbow colorants comprising three carotenoids and four violacein derivatives from glucose or glycerol via systems metabolic engineering and membrane engineering. The research group focused on the production of hydrophobic natural colorants useful for lipophilic food and dyeing garments. First, using systems metabolic engineering, which is an integrated technology to engineer the metabolism of a microorganism, three carotenoids comprising astaxanthin (red), -carotene (orange), and zeaxanthin (yellow), and four violacein derivatives comprising proviolacein (green), prodeoxyviolacein (blue), violacein (navy), and deoxyviolacein (purple) could be produced. Thus, the production of natural colorants covering the complete rainbow spectrum was achieved. When hydrophobic colorants are produced from microorganisms, the colorants are accumulated inside the cell. As the accumulation capacity is limited, the hydrophobic colorants could not be produced with concentrations higher than the limit. In this regard, the researchers engineered the cell morphology and generated inner-membrane vesicles (spherical membranous structures) to increase the intracellular capacity for accumulating the natural colorants. To further promote production, the researchers generated outer-membrane vesicles to secrete the natural colorants, thus succeeding in efficiently producing all of seven rainbow colorants. It was even more impressive that the production of natural green and navy colorants was achieved for the first time. “The production of the seven natural rainbow colorants that can replace the current petroleum-based synthetic colorants was achieved for the first time,” said Dr. Dongsoo Yang. He explained that another important point of the research is that integrated metabolic engineering strategies developed from this study can be generally applicable for the efficient production of other natural products useful as pharmaceuticals or nutraceuticals. “As maintaining good health in an aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” explained Distinguished Professor Lee. This work was supported by the "Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01550602)" Rural Development Administration, Republic of Korea. -Publication:Dongsoo Yang, Seon Young Park, and Sang Yup Lee. Production of rainbow colorants by metabolically engineered Escherichia coli. Advanced Science, 2100743. -Profile Distinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
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